Objectives
The potential of Helicobacter pylori to induce gastric cancer is primarily mediated by the activation of multiple pro-oncogenic pathways by the oncoprotein CagA, which is injected into host epithelial cells. This makes CagA a potential intracellular CD8⁺ T cell antigen. We recently showed that CagA proficient H. pylori strains induce a strong infiltration of  CD8⁺ tissue-resident memory T (T_RM) cells into the murine gastric mucosa. Here, we assessed CagA-specificity and functional properties of murine and human CD8⁺ T cells.
 
Methods
We infect C57BL/6 mice with various CagA-proficient and deficient H. pylori strains and study the gastric immune response natively and after T cell depletion. We analyze gastric biopsies and PBMCs from H. pylori infected patients with and without positive CagA serostatus.
 
Results
In mice, almost all induced gastric CD8⁺ T_RM cells are specific to CagA and respond with release of effector functions including Granzyme B secretion. The recognition of CagA and subsequent IFN-g secretion by CD8⁺ T cells mediates pathogen control in the early infection phase. We corroborate our findings of a CagA-dependent gastric CD8⁺ T_RM cell infiltration in H. pylori infected patients. Importantly, we confirm CagA-specificity in humans and identify multiple CagA-derived CD8⁺ T cell epitopes.
 
 
Conclusions
The recognition of CD8⁺ T cell epitopes derived from a oncoprotein that is injected by an extracellular bacterium is a novel concept in CD8⁺ T cell immunity. It is of huge clinical significance since clearance of CagA-infected epithelium by cytotoxic CD8⁺ T cells could serve as a host protective mechanism to gastric cancer. Thus, CagA-specific CD8⁺ T cells could be of therapeutic use in future.